Impaired dendritic cell maturation and IL-10 production following H. pylori stimulation in gastric cancer patients

The current study was to investigate the interaction between Helicobacter pylori and human dendritic cells (DCs). Whether impaired DC function can influence the outcome of H. pylori infections. Human monocyte-derived DCs (MDDCs) from five gastric cancer patients and nine healthy controls were stimulated with H. pylori. Maturation markers of MDDC were examined by flow cytometry. IL-10 and TNF-α released by MDDCs and IL-17 produced by T cells were measured by ELISA. Regulatory signaling pathways of IL-10 were examined by ELISA, western blotting, and chromatin immunoprecipitation assay. The results showed that as compared with healthy individuals, the maturation marker CD40 in MDDCs, IL-17A expression from T cells, and IL-10 expression from MDDCs were significantly lower in gastric cancer patients. Blocking DC-SIGN, TLR2, and TLR4 could reverse H. pylori-associated IL-10 production. Activation of the p38 MAPK and NF-kB signaling pathways concomitant with decreased tri-methylated H3K9 and increased acetylated H3 accounted for the effect of H. pylori on IL-10 expression. Furthermore, upregulated IL-10 expression was significantly suppressed in H. pylori-pulsed MDDCs by histone acetyltransferase and methyltransferase inhibitors. Taken together, impaired DC function contributes to the less effective innate and adaptive immune responses against H. pylori seen in gastric cancer patients. H. pylori can regulate IL-10 production through Toll-like and DC-SIGN receptors, activates p-p38 MAPK signaling and the transcription factors NF-kB, and modulates histone modification

Does Long-Term Use of Silver Nanoparticles Have Persistent Inhibitory Effect on H. pylori Based on Mongolian Gerbil’s Model?

It is urgent to find alternative agents due to increasing failure rate of Helicobacter pylori (H. pylori) eradication. The study surveyed the long-term effect of silver nanoparticles (AgNP) on H. pylori based on Mongolian gerbil's model

Last-Minute Coordination: Adapting to Demand to Support Last-Mile Operations

In the highly competitive e-commerce industry, customer-facing warehouses are crucial as the “order penetration points” for e-commerce last-mile operations. This research examines how warehouses use last-minute coordination, an unstructured mechanism, to ensure sufficient inventory at the order penetration points. Previous research has focused on structured mechanisms like contracts and inventory management systems to enhance warehouse performance. However, these mechanisms can be ineffective when faced with unforeseen local contingencies. To adjust inventory and adapt to changes in supply and/or demand, warehouses need to engage in unstructured, last-minute coordination with other warehouses. Using coordination and loose coupling theories, we find that coordinating with many warehouses (i.e., large coordination scope) reduces the operational efficiency of individual warehouses. At the network level, we find that a centralized coordination structure improves the operational efficiency of the entire network. We also show that demand uncertainty reinforces the existing last-minute coordination patterns, using the Separable Temporal Exponential Random Graph Model (ST-ERGM). This research highlights the importance of last-minute coordination and reveals its effects on both individual warehouses and the overall network

Fumarate Analogs Act as Allosteric Inhibitors of the Human Mitochondrial NAD(P)+-Dependent Malic Enzyme

Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P)-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P)-ME_R67A/R91A and m-NAD(P)-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P)-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P)-ME enzyme activity

Toward the next generation of air quality monitoring: Persistent organic pollutants

AbstractPersistent Organic Pollutants (POPs) are global pollutants that can migrate over long distances and bioaccumulate through food webs, posing health risks to wildlife and humans. Multilateral environmental agreements, such as the Stockholm Convention on POPs, were enacted to identify POPs and establish the conditions to control their release, production and use. A Global Monitoring Plan was initiated under the Stockholm Convention calling for POP monitoring in air as a core medium; however long temporal trends (>10 years) of atmospheric POPs are only available at a few selected sites. Spatial coverage of air monitoring for POPs has recently significantly improved with the introduction and advancement of passive air samplers. Here, we review the status of air monitoring and modeling activities and note major uncertainties in data comparability, deficiencies of air monitoring and modeling in urban and alpine areas, and lack of emission inventories for most POPs. A vision for an internationally-integrated strategic monitoring plan is proposed which could provide consistent and comparable monitoring data for POPs supported and supplemented by global and regional transport models. Key recommendations include developing expertise in all aspects of air monitoring to ensure data comparability and consistency; partnering with existing air quality and meteorological networks to leverage synergies; facilitating data sharing with international data archives; and expanding spatial coverage with passive air samplers. Enhancing research on the stability of particle-bound chemicals is needed to assess exposure and deposition in urban areas, and to elucidate long-range transport. Conducting targeted measurement campaigns in specific source areas would enhance regional models which can be extrapolated to similar regions to estimate emissions. Ultimately, reverse-modeling combined with air measurements can be used to derive “emission” as an indicator to assess environmental performance with respect to POPs on the country, region, or global level

Rapid identification of allergenic and pathogenic molds in environmental air by an oligonucleotide array

<p>Abstract</p> <p>Background</p> <p>Airborne fungi play an important role in causing allergy and infections in susceptible people. Identification of these fungi, based on morphological characteristics, is time-consuming, expertise-demanding, and could be inaccurate.</p> <p>Methods</p> <p>We developed an oligonucleotide array that could accurately identify 21 important airborne fungi (13 genera) that may cause adverse health problems. The method consisted of PCR amplification of the internal transcribed spacer (ITS) regions, hybridization of the PCR products to a panel of oligonucleotide probes immobilized on a nylon membrane, and detection of the hybridization signals with alkaline phosphatase-conjugated antibodies.</p> <p>Results</p> <p>A collection of 72 target and 66 nontarget reference strains were analyzed by the array. Both the sensitivity and specificity of the array were 100%, and the detection limit was 10 pg of genomic DNA per assay. Furthermore, 70 fungal isolates recovered from air samples were identified by the array and the identification results were confirmed by sequencing of the ITS and D1/D2 domain of the large-subunit RNA gene. The sensitivity and specificity of the array for identification of the air isolates was 100% (26/26) and 97.7% (43/44), respectively.</p> <p>Conclusions</p> <p>Identification of airborne fungi by the array was cheap and accurate. The current array may contribute to decipher the relationship between airborne fungi and adverse health effect.</p

A New Era in Human Factors Engineering: A Survey of the Applications and Prospects of Large Multimodal Models

In recent years, the potential applications of Large Multimodal Models (LMMs) in fields such as healthcare, social psychology, and industrial design have attracted wide research attention, providing new directions for human factors research. For instance, LMM-based smart systems have become novel research subjects of human factors studies, and LMM introduces new research paradigms and methodologies to this field. Therefore, this paper aims to explore the applications, challenges, and future prospects of LMM in the domain of human factors and ergonomics through an expert-LMM collaborated literature review. Specifically, a novel literature review method is proposed, and research studies of LMM-based accident analysis, human modelling and intervention design are introduced. Subsequently, the paper discusses future trends of the research paradigm and challenges of human factors and ergonomics studies in the era of LMMs. It is expected that this study can provide a valuable perspective and serve as a reference for integrating human factors with artificial intelligence.Comment: 14 pages, journal pape